Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas
Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas
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DOI：
10.1097/01.pas.0000176432.73455.1b
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发表时间：
2006-02-01
影响因子：
5.6
通讯作者：
Nikiforov, YE
中科院分区：
文献类型：
--
作者：
Adeniran, AJ;Zhu, ZW;Nikiforov, YE
乳头状癌是甲状腺恶性肿瘤的最常见类型。最近已经显示，这些肿瘤通常具有三种遗传改变之一：BRAF点突变，RET/PTC重排或RAS点突变。在这项研究中，我们分析了这些改变与乳头状癌的微观特征，它们的临床特征和预后特征之间的关系。研究了97个乳头状癌；在所有情况下，都可以用于核酸提取。在96例未选择的病例中，BRAF为42％，RET/PTC为18％，RAS突变为15％。在61例病例中详细评估了形态学特征和6个特征性核特征，并定量评估了3个其他微观特征。在每个肿瘤中至少发现了4个核特征，核假肿块是所有突变组中最不常见的发现。 BRAF突变与较老的患者年龄，典型的乳头状外观或高个子细胞变体，较高的肌外运动延伸率以及表现时更晚期的肿瘤阶段有关。 RET/PTC重排在年龄较小，主要具有典型的乳头状组织学，频繁的PSAMMOMA体和高淋巴结转移率。具有PAS突变的肿瘤仅是乳头状癌的卵泡变体，与明显较小的突出核特征和低淋巴结转移速率相关。这些发现表明，BRAF RET/PTC和RAS突变与甲状腺乳头状癌的不同显微镜，临床和生物学特征有关。
Papillary carcinoma is the most common type of thyroid malignancy. It has been recently shown that these tumors commonly have one of three genetic alterations: BRAF point mutations, RET/PTC rearrangements, or RAS point mutations. In this study, we analyze the relationship between these alterations and the microscopic features of papillary carcinomas, their clinical features, and prognostic characteristics. Ninety-seven papillary carcinomas were studied;, in all cases, frozen tissue was available for nucleic acid extraction. Of 96 unselected cases, 42% were positive for BRAF, 18% for RET/PTC, and 15% for RAS mutations. Morphologic features were evaluated in detail in 61 cases and 6 characteristic nuclear features and 3 additional microscopic features were assessed quantitatively. At least 4 nuclear features were found in each tumor, with nuclear pseudoinclusions being the least frequent finding in all mutation groups. BRAF mutations were associated with older patient age, typical papillary appearance or the tall cell variant, a higher rate of extrathyroidal extension, and more advanced tumor stage at presentation. RET/PTC rearrangements presented at younger age and had predominantly typical papillary histology, frequent psammoma bodies, and a high rate of lymph node metastases. Tumors with PAS mutations were exclusively the follicular variant of papillary carcinoma and correlated with significantly less prominent nuclear features and low rate of lymph node metastases. These findings demonstrate that BRAF RET/PTC, and RAS mutations are associated with distinct microscopic, clinical, and biologic features of thyroid papillary carcinomas.